Study: Engineered airborne hybrid flu contagious between mammals

Critics slam researchers for being "appallingly irresponsible."

Virologists in China have published a paper detailing how they created more than 100 hybrid viruses from H5N1 and the H1N1 strain that caused the deadly swine flu pandemic of 2009. The virologists wanted to see if any combinations would transmit between mammals—five did.

The study, published in the journal Science, comes exactly a year after the release of a controversial paper describing how the H5N1 bird flu could theoretically be modified to become human-contagious. At that time, the international community had called for a moratorium on similar research because of threats related to the virus escaping or the information being used for deadly purposes. Various outbreaks of H1N1 have, over the years, proven extremely dangerous. However, researchers argue we need to learn more about how these viruses mutate, and indeed how hybrids form in nature, to better tackle any future outbreaks.

The process by which hybrids form is known as reassortment, and it occurs when an individual is infected with two different strains. Genetic information is exchanged across the two to form a new and unique virus, exactly what happened in 2009 when a combination of different swine, avian, and human flus from across the globe merged. H1N1 in particular seems to reassort more readily and is highly infectious among humans. On the other hand, H5N1 (bird flu) is not typically infectious. The premise behind the study was to see if hybrids could create a more infectious strain of H5N1.

According to a report by Nature, the team, led by Hualan Chen of the Harbin Veterinary Research Institute of the Chinese Academy of Sciences, created 127 different reassortment viruses by mixing seven specific chunks of genetic information from both H5N1 and H1N1. They then directly infected mice with the virus and tested 19 of the different reassortments on guinea pigs. After leaving infected guinea pigs in cages alongside uninfected ones, the team found that "the H5N1 hybrid viruses bearing one or more of the PA, NA, M, or NS genes of 2009/H1N1 were transmissible" through the air. This, they say, demonstrates that H5N1 has the potential to be transferred between humans.

"Since the internal genes of these reassortants can already replicate efficiently in mammalian hosts, we predict that similar reassortants could infect humans and subsequently acquire mutations that improve binding efficacy."

It's worth noting that guinea pigs, though mammals, contain both avian and mammalian receptors. The results would be far different in humans. Furthermore, none of the guinea pigs died, but some mice directly infected with the viruses did. It's also important to acknowledge that Chen carried out the research prior to when the moratorium was put in place.

Yet despite this, the argument that we should be prepared for all kinds of natural reassortment, the fact that the study was carried out in China's high-security National Avian Influenza Reference Laboratory at Harbin Veterinary Research Institute (biosafety level 3), and the fact that China—which is currently experiencing a deadly outbreak of the H7N9 bird flu strain—is all too well aware of the potential dangers, critics have already come out to slam the researchers for being "appallingly irresponsible" and "driven by blind ambition."

The critiques were the focus of a piece on the study by the IndependentFriday, in which Robert May, formerly chief scientific advisor to the government, came out with the aforementioned harsh responses. "The record of containment in labs like this is not reassuring," he continued. "They are taking it upon themselves to create human-to-human transmission of very dangerous viruses. It's appallingly irresponsible."

Also speaking to the Independent, virologist Simon Wain-Hobson of the Pasteur Institute in Paris commented: "It's a fabulous piece of virology by the Chinese group and it's very impressive, but they haven't been thinking clearly about what they are doing. It's very worrying. The virological basis of this work is not strong. It is of no use for vaccine development and the benefit in terms of surveillance for new flu viruses is oversold." Wain-Hobson may be referring to the fact that the study was done on guinea pigs, not the ideal stand in for a human study. The Chinese team was, however, apparently planning on trialing the viruses on ferrets, which would help represent a closer model for human flu.

Back in 2009 shortly after the outbreak of the reassorted H1N1 virus, the US Centers for Disease Control and Prevention mixed the H1N1 and H5N1 virus, so Chen is far from the first to attempt this. Not only that, the US study was done with ferrets.

Andrew Pekosz, a virologist at Johns Hopkins Bloomberg School of Public Health, told CIDRAP News that he sees work like the Chinese team's as essential: "The more we understand how wide-ranging those combinations of genetic changes are that can lead to this kind of transmission, the better off we'll be. That knowledge helps inform us what we should be looking for regarding viruses that are potential human pathogens."

Pekosz added that he believed, from what he knew, the team took all safety concerns into account at the same standard as a US lab. He also pointed out that there's no way we can know if the same reassortments would ever naturally occur.

It does seem, however, that the lifting of the moratorium does not sit well with many in the community.

I live within easy walking distance of the Centers for Disease Control's main campus. If a super-bug ever escapes from the CDC's high-containment laboratories, I'll be among the first to get it. I am far more worried about my drive up I-75 every day.

Research into communicable diseases conducted responsibly in properly equipped laboratories is what's going to save us (if anything does) should such agents ever occur in the wild. It doesn't make any difference whether they occur naturally or as the result of some madman trying to make a weapon. Don't forget that these Chinese researchers would be among the first to get the disease if they were not appropriately careful. The fact that their work is published gives me a fair amount of comfort that they're doing exactly what they claim to be doing.

I have to add the disclaimer that I'm a computer scientist, not a virologist.

I struggle to think of a more potentially dangerous research topic (in terms of fatality risk to the largest number of humans in the case of a accident or containment incident) in any field of science. Combined with the questionable value of the study, I find it hard to justify this research in any way.

I am absolutely in favor of viral research, but there's no reason to take unnecessary risks. If the researchers wanted to study reassortment they could have used two viral strains that posed a lot less natural risk to humans, rather than trying to hybridize one strain known to be *highly contagious* in humans with one known to be *highly fatal* in humans.

So... what new defensive mechanisms have we learned from this "research"?

Directly? Probably none. If you want 'new defensive mechanisms' within one research round you pretty much farm it out the vaccine guys(just like we do every. single. year. which is why people are getting frustrated with that plan).

I assume that the mid to long-term game is to try to amass information on how the viral recombination works, and what traits do or don't make it mammal-transmissible, so as to improve the accuracy and lead time of the present(somewhat crude) "Hang around China swabbing sick ducks and pigs in the hopes that we can predict what strain will be cool 8 months from now so that the vaccine we develop for this year actually works" technique.

Of course, the "Why didn't they just call the paper 'Apparatus and Methods for Rapid Prototyping of Mammalian Pandemic Influenza Strains' and have done with it?" does sort of write itself...

You may be right; I'm not a virologist, but I have a hard time understanding how we (previously) knew anything about a strain of flu that had not previously existed.

Regarding transmission, once it infects humans, we know everything there is to know. Direct contact, proximity and being in contact with surfaces an infected person has contaminated. These are not cutting edge pieces of data.

You may be right; I'm not a virologist, but I have a hard time understanding how we (previously) knew anything about a strain of flu that had not previously existed.

Regarding transmission, once it infects humans, we know everything there is to know. Direct contact, proximity and being in contact with surfaces an infected person has contaminated. These are not cutting edge pieces of data.

That doesn't follow. If we truly knew "everything there is to know" about viruses that infected humans, we'd have a cure for the common cold, not to mention things like AIDS.

Beyond that, as far as I can tell from the article, the strains (reassortments) described in the study have never infected humans. A huge part of the fear is that they might escape from the laboratory (or be similarly engineered elsewhere) and might then infect humans.

You may be right; I'm not a virologist, but I have a hard time understanding how we (previously) knew anything about a strain of flu that had not previously existed.

Regarding transmission, once it infects humans, we know everything there is to know. Direct contact, proximity and being in contact with surfaces an infected person has contaminated. These are not cutting edge pieces of data.

That doesn't follow. If we truly knew "everything there is to know" about viruses that infected humans, we'd have a cure for the common cold, not to mention things like AIDS.

Beyond that, as far as I can tell from the article, the strains (reassortments) described in the study have never infected humans. A huge part of the fear is that they might escape from the laboratory (or be similarly engineered elsewhere) and might then infect humans.

He clearly meant: Everything there is to know by doing this specific research study.

i wonder if this has anything to do with the 16000 dead pigs found in the Yangtze River?no, that would be silly

Yes, that would be silly.

Aside from the fact that they didn't use pigs at all, you're assuming that a highly trained, educated group of professionals have deliberately placed 16000 carcasses filled with an extremely infectious, highly lethal contagion in one of the most densely populated regions on Earth.

Or do those critics believe that deliberate ignorance is a superior virtue?

Ignoring the fact that any knowledge gained from this would be minor while simultaneously making a DIY guide for creating pandemics? When there are far safer ways to do the same research with the same benefits, then yes.

Or do those critics believe that deliberate ignorance is a superior virtue?

Ignoring the fact that any knowledge gained from this would be minor while simultaneously making a DIY guide for creating pandemics? When there are far safer ways to do the same research with the same benefits, then yes.

1. that's been publically available knowledge for at least a decade already, another few decades in the military

2. bio 3/4 is pretty much as safe as you can get. this was conducted at a reputable institution in this field

1) Whenever there's a flu outbreak we struggle to identify the strain and then form a vaccine against it. Using this method we can pre-determine what the more virulent and serious strains of influenza are and then work toward having vaccines already assembled.

2) Have you ever wondered why you need a different influenza vaccine every year? It's because of the mixing and matching that occurs, and the vaccine is a "best guess" as to what assortments we might encounter in the coming year. If we know what the more serious strains are without having experienced their impacts on the population then we could possibly add that in to the yearly vaccine as well. Even if the chances of encountering it in nature are low, better safe than sorry.

Bonus: 3) Seeing how the mixing and matching occurs and determining which strains seem to spread better or have more severe affects can always be useful in terms of predicting the viral flow in the environment and determining how and when certain strains will come about.

It's amazing how much the C word (China) changes people's tone. It's the how not the where. What do they need to do to prove themselves in this field? Do you honestly think it's some old fisherman in a rice paddy mixing viruses? Seriously....

I don't know where you're gettting this. The whole concept of an ethnic group is basically a false construct, but there are groups of people who have unique genetic differences and immunities passed down from their mothers.

Here's one: Look anywhere in medical documentation and find a disease that is said to "only affect X ethnicity."

Go ahead. Find one. A single one. I'll be sitting here eating crackers while you try.

I'll limit my answer in two ways. I focus on just infection by distinct pathogens, which is the only sensible focus of this question. I'll also limit by ignoring pathogens that some groups are susceptible to merely due to lack of exposure, rather than inherent differences. Those limitations exclude everything Glitch's post right before mine brings up, but it does refer to something relevant . . .

The easy example is that people of (recent, to be pedantic) African descent are often less susceptible to malaria. The biological basis for this is that those same people much more often carry the mutations that cause sick-cell anemia. That mutation, whether heterozygous (genetic carrier only) or homozygous (actual sufferer of sickle-cell anemia) also makes it harder for malaria to infect the cells in question.

It's amazing how much the C word (China) changes people's tone. It's the how not the where. What do they need to do to prove themselves in this field? Do you honestly think it's some old fisherman in a rice paddy mixing viruses? Seriously....

Having a history of cutting-corners (in general) doesn't help China's reputation. There's also the issue of different regulatory barriers when it comes to research. Hopefully self-preservation helps in all this.

So... what new defensive mechanisms have we learned from this "research"?

Well, if it turns out that one particular mutation is always required for mammal to mammal transmissibility then it would be a good idea to monitor animal and human populations for that mutation. The virus can mutate in any way imaginable, but only a small number of those ways will be viable and this type of research further restricts the mutations we're most interested in.

Also, they only made virus able to transmit guinea pig to guinea pig. So why is everyone getting their knickers in a knot? Personally I think that politicians and journalists sensationalising an important application of the scientific method is the despicable and irresponsible part. Just like they did to climate change - and look what they've managed to achieve there.

It's amazing how much the C word (China) changes people's tone. It's the how not the where. What do they need to do to prove themselves in this field? Do you honestly think it's some old fisherman in a rice paddy mixing viruses? Seriously....

Having a history of cutting-corners (in general) doesn't help China's reputation. There's also the issue of different regulatory barriers when it comes to research. Hopefully self-preservation helps in all this.

Are you kidding? The Chinese Academy of Sciences is highly respected in the world. Any scientist worth their salt recognizes that. The quoted researchers in The Independent were hiding their racism behind false worries of outbreaks. The fact is that when this type of research was done by Europeans a few years back the response was much more diplomatic. It is extremely refreshing to see this article have a quote from an American researcher saying that this work is important. There are journal snobs out there, but the fact that this paper was published in Science means that the work was rigorously vetted. We need *more* scientists that can do this type of high-quality work, not less. They did this work *prior* to the moratorium, and since then nobody has died. As stated by the article, the CDC has already done this type of work long ago. Again, nobody died. So any fears that you may have is completely manufactured by the media.

Im also confused by the anti research group. Knowledge gained in a safe way is a good thing. People die every year from the flu and hit hits china exceptionally hard so any advantage they can get is great. Are people worried about people breaking in and stealing the strain? Or are they worried about someone creating it for use as a weapon? If its the latter you need to realize that it takes a pretty sophisticated lab and if a terrorist cell has a lab like this then we have much bigger problems. If you're worried about a government doing it for a weapon they'll do it anyway and they sure as hell wont be publishing their results.

Im also confused by the anti research group. Knowledge gained in a safe way is a good thing. People die every year from the flu and hit hits china exceptionally hard so any advantage they can get is great. Are people worried about people breaking in and stealing the strain? Or are they worried about someone creating it for use as a weapon? If its the latter you need to realize that it takes a pretty sophisticated lab and if a terrorist cell has a lab like this then we have much bigger problems. If you're worried about a government doing it for a weapon they'll do it anyway and they sure as hell wont be publishing their results.

How about accidents happening, or have labs become "too sophisticated" for that to happen?

Engineer the virus(es) so it is only certain groups of humans get infected...this may be currently a bit beyond the state of the genetic art but for how long I wonder?

and then...

Lo and Behold! the world is made safe for the group who does NOT get infected.

For one, diseases with extremely high short-term lethality don't become worldwide epidemics because the host will die before they can spread the disease. If such a thing were to become apparent, western governments would simply quarantine the fuck out everybody who was remotely exposed. You'd have a high short-term economic loss, but it would be contained. If this were an attack against a weaker enemy, you might wipe them out, but then you still run into the following issue if they found out you did it....

If you made sure that the disease had a good incubation period so that the vector can travel along and expose as many as possible before surely dying, you'd run into another problem: extreme social unrest. This starts at rioting if it's clear that certain people are never getting sick (and with the media, you can bet people would find out), and goes up to nuclear war, depending on who you target, because the idea of mutually-assured-destruction means nothing if you're gonna die regardless.

To counter these problems you'd need a convention attack as well, and that would carry all the usual problems of a conventional attack combined with acquiring the moral standing of Adolf Hitler. So no matter what you're not gonna be safe if you do something like this; people won't just stand around and say "oh, well, we're gonna die, I guess let's leave those guys alone", and if they're not able to stand around, the uninfected will avoid them.

Essentially: weaponized disease is fucking stupid in this day and age.

Im also confused by the anti research group. Knowledge gained in a safe way is a good thing. People die every year from the flu and hit hits china exceptionally hard so any advantage they can get is great. Are people worried about people breaking in and stealing the strain? Or are they worried about someone creating it for use as a weapon? If its the latter you need to realize that it takes a pretty sophisticated lab and if a terrorist cell has a lab like this then we have much bigger problems. If you're worried about a government doing it for a weapon they'll do it anyway and they sure as hell wont be publishing their results.

How about accidents happening, or have labs become "too sophisticated" for that to happen?

Labs are far more sophisticated than the natural environments where these things tend to happen regardless of the actions of researchers. If you're expecting someone to prove a negative, I'd love to, but I need to get out of my house before the roof caves in; the architect and builders didn't show me all their work, so how can I know it won't happen?

Are you kidding? The Chinese Academy of Sciences is highly respected in the world. Any scientist worth their salt recognizes that.

You are grossly overselling this and making a baseless appeal to authority. The Chinese Academy of Sciences is HUGE in terms of the number of researchers it supports and counts as members (incl. many US based academics who don't directly work for the Academy). And as with any large group of people, the quality of the work published ranges from rubbish to great.

The fact the researchers for this particular work are affiliated with the Chinese Academy says nothing about the quality of the work.

Heh. That's pretty much China, ever since they came out of their self-deprivation mindset.

Quote:

fraoch wrote:i wonder if this has anything to do with the 16000 dead pigs found in the Yangtze River?no, that would be silly

Shimme responed:Yes, that would be silly.

Aside from the fact that they didn't use pigs at all, you're assuming that a highly trained, educated group of professionals have deliberately placed 16000 carcasses filled with an extremely infectious, highly lethal contagion in one of the most densely populated regions on Earth.

Well, in fairness, you filled all that last part in. As the study shows, it's not trivial for an infection to jump species. So what killed 16000 pigs has a good chance of not even being infectious to humans. And I don't think anybody thought it was real scientists that dumped them like that.

But all those pigs caught *something*, didn't they? It's not so silly to remember it, in a discussion of deadly flus that jump species.

Im also confused by the anti research group. Knowledge gained in a safe way is a good thing. People die every year from the flu and hit hits china exceptionally hard so any advantage they can get is great. Are people worried about people breaking in and stealing the strain? Or are they worried about someone creating it for use as a weapon? If its the latter you need to realize that it takes a pretty sophisticated lab and if a terrorist cell has a lab like this then we have much bigger problems. If you're worried about a government doing it for a weapon they'll do it anyway and they sure as hell wont be publishing their results.

How about accidents happening, or have labs become "too sophisticated" for that to happen?

Labs are far more sophisticated than the natural environments where these things tend to happen regardless of the actions of researchers. If you're expecting someone to prove a negative, I'd love to, but I need to get out of my house before the roof caves in; the architect and builders didn't show me all their work, so how can I know it won't happen?

You can have a home inspector or engineer take a look at it, of course. And if your cave-in was at all likely to cause an epidemic of cave-ins, you would do so. And we would be careful to train homeowners to regularly inspect their roofs.

Certainly accidental exposures into the community happen -- for example, with Marburg, and Anthrax.

The most significant result which emerges from these studies is that they were performed approximately twenty years apart. During this period all of the concepts for laboratory safety, including safety procedures practices, personnel protection, the use of chemical fume hoods and biosafety cabinets, etc. were introduced into the laboratory work place. This would suggest that laboratory safety with potentially hazardous biological materials is more than having these safety resources available. Most experts agree that it is the proper implementation, use and training of laboratory workers that are the essential elements to prevent laboratory associated illness.

I am not arguing against research into pathogens at all, but we have to keep in mind that this work has both rewards and risks.